Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors.
We prepared methyl 2,5-dihydroxycinnamate as a stable analogue of erbstatin, a tyrosine kinase inhibitor. This analogue was about 4 times more stable than erbstatin in calf serum. It inhibited epidermal growth factor receptor-associated tyrosine kinase in vitro with an IC50 of 0.15 micrograms/ml. It also inhibited in situ autophosphorylation of epidermal growth factor receptor in A431 cells. Methyl 2,5-dihydroxycinnamate was shown to delay the S-phase induction by epidermal growth factor in quiescent normal rat kidney cells, without affecting the total amount of DNA synthesis. The effect of erbstatin on S-phase induction was smaller, possibly because of its shorter life time.
Umezawa
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Hori
T
T
Tajima
H
H
Imoto
M
M
Isshiki
K
K
Takeuchi
T
T
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D006873:Hydroquinones; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D013936:Thymidine; C048212:erbstatin